Organ Regeneration

The laboratories in the Dept. of Developmental Biology have a strong focus on organ regeneration. Faculty are interested in understanding the molecular mechanism that drives the regenerative process in heart (Tsang), liver (Shin) and kidney (Hukriede). Our studies use the zebrafish animal model as a vertebrate that is endowed with remarkable regenerative abilities and combine with genetic and chemical biology approaches to understand the regeneration.

Dusp6 mutant hearts exhibit increased cardiomyocyte proliferation after ventricular resection. Taken from Missinato et. al. Development 2018.

 

A zebrafish liver injury model for biliary epithelial cell-driven liver regeneration.  Metronidazole (Mtz) was applied from 3.5 to 5 days post-fertilization (dpf) for 36 hours. The Mtz treatment greatly reduced liver size and fabp10a:CFP and fabp10a:dsRed fluorescence at R0h; however, strong CFP and dsRed fluorescence reappeared at R30h, indicating rapid liver regeneration. (Taken from Choi et. al. J. Vis. Exp. 2015)

 

Selected Publications:

Hdac1 regulates differentiation of bipotent liver progenitor cells during regeneration via Sox9b and Cdk8.
Ko S, Russell JO, Tian J, Gao C, Kobayashi M, Feng R, Yuan X, Shao C, Ding H, Poddar M, Singh S, Locker J, Weng HL, Monga SP, Shin D.
Gastroenterology. (2019) 156(1):187-202. PMCID: PMC6309465
[Abstract]
 
A zebrafish larvae model to study the role of innate immunity in septic acute kidney injury.
Wen, W., Cui, L., Morrisroe, S., Maberry, D., Emlet., D., Watkins, S., Hukriede, N.A., Kellum, J.  
AJP-Renal Physiology (2018) Aug 1:315(2):F291-299. PMCID: PMC6139521
 
Dusp6 attenuates Ras/MAPK signaling to limit zebrafish heart regeneration.
Missinato MA, Saydmohammed M, Zuppo DA, Rao KS, Opie GW, Kühn B, Tsang M.
Development. 2018 Mar 6;145(5). 
 
Bmp signaling governs biliary-driven liver regeneration in zebrafish via Tbx2b and Id2a. 
Choi TY, Khaliq M, Tsurusaki S, Ninov N, Stainier DY, Tanaka M, Shin D. 
Hepatology, (2017) 66:1616-1630. PMCID: PMC5650528
[Abstract]
 
Bromodomain and extraterminal domain (BET) proteins regulate biliary-driven liver regeneration
Ko S, Choi TY, Russell JO, So J, Monga SP, Shin D.
J Hepatology, (2016) 64:316-25. PMCID: PMC4718879
[Abstract]
 
A genetically targetable near-infrared photosensitizer.
He J, Wang Y, Missinato MA, Onuoha E, Perkins LA, Watkins SC, St Croix CM, Tsang M, Bruchez MP.
Nat Methods. 2016 Mar;13(3):263-8
 
Delayed treatment with PTBA analogues reduces post injury renal fibrosis after kidney injury.
Skrypnyk, N. I., Sanker, S., Brilli Skvarca, L., Woods, C., Chiba, T., Patel, K., Goldberg, N. D., McDermott, L., Vinson, P. N., Calcutt, M. W., Vernetti, L. A., Vogt, A., Huryn, D. M., Hukriede, N. A., and M. P. de Caestecker. 
AJP-Renal Physiology (2016) 310: F705-16. PMCID: PMC4835925
 
Extracellular component hyaluronic acid and its receptor Hmmr are required for epicardial EMT during heart regeneration.
Missinato MA, Tobita K, Romano N, Carroll JA, Tsang M.
Cardiovasc Res. 2015 Sep 1;107(4):487-98
 
Extensive conversion of hepatic biliary epithelial cells to hepatocytes after near total loss of hepatocytes in zebrafish.
Choi TY, Ninov N, Stainier DY, Shin D.
Gastroenterology,  (2014) 146(3):776-788. PMCID: PMC3943869
[Abstract]
 
Histone Deacetylase inhibitor enhances recovery after AKI.
Cianciolo Cosentino, C, Skrypnyk, N., Brilli L.B., Chiba, T., Novitskaya, T., Woods, C., West, J., Korotchenko, V.N., McDermott, L., Day, B.W., Davidson A.J., Harris, R., de Caestecker, M.P., and N.A. Hukriede
JASN (2013) May 26(6), 943-53. PMCID: PMC3665399